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. 1990 Feb;81(2):196–200. doi: 10.1111/j.1349-7006.1990.tb02548.x

Prediction from Creatinine Clearance of Thrombocytopenia and Recommended Dose in Patients Receiving (Glycolato‐O, O′)‐diammine Platinum (II) (NSC 375101D)

Yasutsuna Sasaki 1,✉, Masaaki Fukuda 1, Masashige Morita 1, Tetsu Shinkai 1, Kenji Eguchi 1, Tomohide Tamura 1, Yuichiro Ohe 1, Kohzo Yamada 1, Akira Kojima 1, Kazuhiko Nakagawa 1, Toru Ohmori 2, Nagahiro Saijo 1,2
PMCID: PMC5963895  PMID: 2110134

Abstract

Thrombocytopenia is the most serious dose‐limiting toxicity of (glycolato‐O, O′)‐diammine platinum (II) (254‐S; NSC 375101D), one of the new platinum analogues. A total of 38 patients treated with 100 mg of 254‐S per m2 in a clinical phase II study were retrospectively analyzed to determine the factors influencing thrombocytopenia. Performance status, sex, age and prior chemotherapy did not affect either the percent reduction of platelets or the nadir platelet count. However, creatinine clearance (Ccr.: ml/min) was found to be a predictive variable for thrombocytopenia. There was a significant relationship between nadir platelet count and Ccr. (R2=0.637) or relative dose [RD = (dose of 254‐S: mg/m2)/Ccr.] (R2= 0.707). From these observations, the following equations for predicting nadir platelet count associated with administration of 254‐S were proposed.

graphic file with name CAS-81-196-e001.jpg (A)
graphic file with name CAS-81-196-e002.jpg (B)

If we administer 100 mg of 254‐S per m2 to a patient with Ccr. of less than 40.3 ml/min, thrombocytopenia of grade 3 or more according to the Eastern Cooperative Oncology Group (ECOG) criteria (< 50,000/mm3) can be predicted from equation (A). In these patients, dose modification using equation (B) is recommended.

Keywords: Cisplatin, 254‐S, Area under the curve, Pharmacokinetics/pharmacodynamics

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